A successful evaluation of anti-caries immunity is dependent upon a suitable animal model with well defined parameters including: a) the immune response (IR), including immunoglobulin levels and specific antibodies; b) pathogenesis of the test bacterium; c) susceptibility of the animal to caries attack and d) the specificity of caries attack. Antibiotic-suppressed (A.S.) and gnotobiotic rats infected with certain S. mutans groups and mutants have provided two such caries models for our studies. These investigations have been concerned with 1) evaluation of effective methods for induction of caries immunity and 2) characterization of mechanisms involved in this immunity. In earlier studies we have shown that local injection of killed S. mutans induces salivary IgA antibody and this correlates with caries protection from subsequent challenge with the homologus S. mutans. Subsequent studies in this laboratory have indicated that a similar s-IgA response and caries protection can be achieved in gnotobiotic rats that ingest S. mutans antigen. Since it is quite unlikely that local salivary gland injections can be achieved in human subjects, current research is concentrating on better characterization of the IR following oral immunization. Dosages and schedules of administration necessary for achieving this optimal response are being investigated. The mechanisms of this antigenic stimulation, including localization of antigen stimulated cells, homing of these cells to secretory tissue including mammary and salivary glands and subsequent antibody production in saliva and milk are being considered. Since non-specific immune factors can play an important role in caries protection, the effect of immunization on the salivary levels of lysozyme, lactoferrin and lactoperoxidase are being determined. In conjunction with these in vivo assays, in vitro studies are being initiated to investigate possible antibacterial effects of the interactions between purified s-IgA and lactoferrin, lysozyme and lactoperoxidase. BIBLIOGRAPHIC REFERENCES: McGhee, J.R., Michalek, S.M., Webb, J., Navia, J.M., Rahman, A.F.R. and Legler, D.W. Effective immunity to dental caries: Protection of gnotobiotic rats by local immunization with Streptococcus mutans. J. Immunol., 114: 300, 1975.